The Medicinal Chemistry and Lead Development Core (MCLDC) is a key component of the Antiviral Drug Discovery and Development Center (AD3C) that will contribute to the goals of the overall Center of Excellence for Translational Research (CETR) program to develop new replication inhibitors and other broad-based therapeutics for the treatment of emerging pathogens through its interaction with each of the individual projects and cores. The MCLDC will provide a) synthetic chemistry, b) structure-activity relationship (SAR) data and analysis, c) lead optimization chemistry, d) bioanalytical assays, e) structural biology and computational support, and d) compound storage and data management. In this role, the MCLDC, in conjunction with the Assay Core, will be the central focus of the translational research component of the program. As such, the MCLDC will work closely with the Assay Core and each of the Research Project teams. As new chemical entities are designed and synthesized during the lead generation and optimization processes, the Assay Core will test these analogs in SAR-driving assays. Testing of compounds for drug-like properties such as microsomal stability and solubility; and in vitro Absorption, Distribution, Metabolism and Excretion (ADME) will be an integral part of SAR studies from the early developmental phase. Appropriate lead compounds will be provided to the various Research Project teams for advanced studies including efficacy, mechanism of action, and other experiments. The resulting data on lead compounds from the Assay Core and Research Projects will then be analyzed by the MCLDC to drive the iterative lead optimization and in vivo PK studies to completion, resulting in optimized leads with drug-like properties for animal studies. The lead candidates will have met the go/no go decision criteria set for activity, potency and drug-like properties. The goal for the end result of this process will be identification of novel optimized lead molecules that are appropriate for IND applications. The MCLDC will incorporate key personnel of other Cores and Research Project teams into the prioritization and decision?making procedures.